Pratique clinique Clinical Pract ice
G
estational diabetes aff ects an estimated 20%of pregnant women during the third trimester.
Untreated, this condition is associated with fetal macrosomia and increased rates of perinatal death and complications.1 The hallmark of therapy for gestational diabetes is a low-carbohydrate diet and, when needed, injectable insulin.2
Studies have shown that tight control of mater- nal glucose levels is associated with favourable pregnancy outcomes.2 Tight control, however, is hampered by poor compliance due to both the high level of discipline demanded from patients and the prohibitive cost of insulin and injection parapher- nalia.3 It is fair to assume that women in developing countries and poor women in developed countries can rarely aff ord such a regimen.
Th e main objection to using oral hypoglycemics for gestational diabetes is that they cross the human
placenta and can cause hyperinsulinism in unborn babies and subsequently life-threatening neonatal hypoglycemia. Th is has led to sweeping avoidance of this class of drugs during the third trimester.
Two studies by Elliott and associates4 and Langer and colleagues,5 however, changed people’s minds on this issue. Ten years ago, these researchers con- ducted placental perfusion studies that showed that the oral hypoglycemic glyburide does not cross the human placenta in clinically relevant amounts.4 Subsequently, they conducted a trial in which they randomized more than 400 women with gestational diabetes to receive either injectable insulin or oral glyburide.5
The two regimens were similarly effective in treating the condition, had similar rates of birth defects and neonatal morbidity, and resulted in similar birth weights. Glyburide did not cause Gideon Koren, MD, FRCPC
Breakthrough in treating gestational diabetes mellitus
ABSTRACT
QUESTION I practise in a remote community in Manitoba. Quite a few of my patients experience gestational diabetes.
Their compliance with the insulin regimen is abysmal. Can I give them an oral medication?
ANSWER Recent studies have indicated that glyburide does not cross the human placenta and that its eff ectiveness and safety profi les are similar to those of insulin.
RÉSUMÉ
QUESTION J’exerce la médecine dans une collectivité éloignée du Manitoba. Un bon nombre de mes patientes souff rent du diabète gestationnel. Leur conformité avec le régime d’insuline est épouvantable. Puis-je leur prescrire des médicaments par voie orale?
RÉPONSE De récentes études ont démontré que le glibenclamide ne traverse pas le placenta humain et que ses profi ls d’effi cacité et d’innocuité sont semblables à ceux de l’insuline.
Motherisk Update
VOL 50: JULY • JUILLET 2004dCanadian Family Physician • Le Médecin de famille canadien 987
FOR PRESCRIBING INFORMATION SEE PAGE 1050
➛
Pratique clinique Clinical Pract ice
neonatal hypoglycemia. Umbilical cord levels of the drug were undetectable, and maternal levels were within the therapeutic range,5 further con- fi rming results of the in vitro perfusion studies.
Although it is now 3 years later, I am unaware of any study that has repeated this protocol.
Motherisk callers report that, while glyburide is not yet offered in most academic centres, more and more community practitioners are using it.
Moreover, postmarketing registries in Europe and South America have not revealed higher fetal or neonatal risks. Glyburide is a cheap oral medica- tion that circumvents the problems of patient com- pliance with insulin.
The mechanisms preventing glyburide from crossing the human placenta are not completely understood. A combination of very high protein binding (more than 99.8%) and a short elimination half-life might partially explain it. Motherisk is now investigating the hypothesis that glyburide, being a substrate for the placental p-glycoprotein carrier system, might be actively pumped from baby to mother.6
It is also important to note that a study just com- pleted by the Motherisk Program showed that gly- buride, when used at the recommended dose, did not to cross into breast milk.7
References
1. Ben Haroush A, Yogev Y, Hod M. Epidemiology of gestational diabetes mellitus and its association with type 2 diabetes. Diabet Med 2004;21:103-13.
2. Bronkston GN, Mitchell BF, Ryan EA, Okun NB. Resistance exercise decreases the need for insulin in overweight women with gestational diabetes mellitus. Am J Obstet Gynecol 2004;190:188-93.
3. Moses RG, Webb AJ, Comber CD, Walton JG, Coleman KJ, Davis WS, et al. Gestational diabetes mellitus: compliance with testing. Aust N Z J Obstet Gynaecol 2003;43:469-70.
4. Elliott BD, Schenker S, Langer O, Johnson B, Prihoda T. Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer. Am J Obstet Gynecol 1994;171:653-60.
5. Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-8.
6. Garcia-Bournissen F, Feig DS, Koren G. Maternal-fetal transport of hypoglycemic drugs.
Clin Pharmacokinet 2003;42:303-13.
7. Feig DS, Kraemer J, Klein J, Koren G. Transfer of glyburide into breast milk [abstract]. Clin Pharmacol Th er 2004;75:28.
Motherisk Update
Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Dr Koren is a Senior Scientist at the Canadian Institutes for Health Research and holds the Ivey Chair in Molecular Toxicology at the University of Western Ontario in London.
Do you have questions about the safety of drugs, chemi- cals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at (416) 813-7562; they will be addressed in future Motherisk Updates.
Published Motherisk Updates are available on the College of Family Physicians of Canada website (www.cfpc.ca). Some articles are published in The Motherisk Newsletter and on the Motherisk website (www.motherisk.org) also.
...
VOL 50: JULY • JUILLET 2004dCanadian Family Physician • Le Médecin de famille canadien 989
